Vasopressin in dehydrated and rehydrated ponies

Six pony mares deprived of water for 24 hours showed significant increases in plasma vasopressin (2.8 pg/ml) and osmolality (9 mosmol/kg). When water was made available the ponies drank rapidly (5 of 6 drank to satiety within 90 seconds) and corrected their fluid deficits precisely. Vasopressin did not return to predehydration levels until osmolality did after 15 minutes of access to water. The horse differs from rodents and humans, but is similar to pigs in that vasopressin levels do not fall before osmolality returns to normal. Oropharyngeal factors, therefore, may not be as important in vasopressin release in horses as in other species.     

Vasopressin use in shock

Arginine-vasopressin (VP), also known as the antidiuretic hormone, is essential for water homeostasis. Its synthesis and liberation depends on regulation of osmotic, hypovolemic, hormonal, and nonosmotic stimuli. It has been demonstrated that it is key for maintenance of cardiovascular homeostasis through vasomotor regulation, the determinant of systemic vascular resistance and mean arterial pressure, a process acting through V1 receptors. Shock state with refractory vasodilation seen in sepsis, systemic inflammatory response, hypovolemia, cardiac arrest, polytrauma, etc., is characterized by an initial phase of liberation and increased levels of VP followed by a second phase characterized by inappropriately low levels of this hormone that are associated with refractoriness to management with volume, inotropics, and vasopressors. It has been demonstrated in clinical and experimental studies that exogenous VP treatment under this condition increases systemic vascular resistance, perfusion pressure, and oxygen supply to peripheral tissues, which makes it possible to decrease and to suspend vasopressors and also to increase survival.     

Zum Wirkungsmechanismus von Vasopressin

Ohne Zusammenfassung     

Vasopressin studies in the rat

Summary A modification of Jeffers method for estimating antidiuretic hormone in body fluids is described. With this modification it is possible to detect antidiuretic activity corresponding to 0.25 U of Vasopressin.

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Zusammenfassung Eine Modifikation von Jeffers Methode zur Bestimmung von antidiuretischem Hormon in Körperflüssigkeiten wird beschrieben. Diese Modifikation erlaubt, antidiuretische Aktivität in der Größenordnung von 0,25 E Vasopressin festzustellen.

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The work was supported by Grant No. AF EOAR 65–63 U.S. Air Force, Brussels Office, and the Deutsche Forschungsgemeinschaft.     

Vasopressin studies in the rat

Summary In previous experiments single i.v. injections of 0.2–10 U ADH were made in alcohol anesthetized rats and the amount of extra water reabsorbed during the antidiuretic phase (urine deficit) was measured. The dose response curve resembled a saturation curve with a fairly linear rise up to 1–1.5 U. When 4–6 U were injected the urine deficit was not appreciably greater while 75% of the ADH injected appeared in the urine during antidiuresis. It was concluded that during a single injection of ADH 1–1.5 U were bound almost instantaneously at receptors of the tubular wall and inactivated during the slow process of water reabsorption, while the excess ADH was excreted in the urine. It was estimated that 1 U ADH was needed for the reabsorption of approximately 5 cm³ water. The time required for this process is short at a high rate of reabsorption and vice versa.In the present investigation the single i.v. injections were repeated with 20 U. The higher dose permitted the separate determination of ADA in 3 consecutive samples of the urine collected during the antidiuretic phase. The result fully confirmed the working hypothesis e.g.:1. The antidiuretic activity (ADA) obtained with 20 U Pitressin was not greater but even (though not significantly) smaller than that obtained previously with 5 U Pitressin or 1 U Tonephin.2. 95±15% of the ADA injected appeared in the urine. This means that the difference between the 20 U injected and the 18.5–19 U appearing in the urine after deduction of the 1–1.5 U ADH supposedly bound at tubular pore sites was too small to be detected with our bioassay.3. Under the assumption that 1 U Pitressin was used up for the reabsorption of approximately 4 cm³ water a vasopressin-water-equivalent in the order of 1 mole vasopressin for 10⁸ mole water reabsorbed, could be calculated.4. The amount of vasopressin excreted by the kidney follows an exponential function with a half life of 5 min.5. The vasopressin clearance is approximately 1.0 cm³/min · rat and lies within the range of inulin clearance (1.2 cm³/min · rat). It is suggested that elimination of excess vasopressin proceeds by a simple filtration process.6. Calculating on a weight basis the ADH-requirement of the 200 times heavier human kidneys leads to the value 200–300 U. Using a vasopressin-water-equivalent of 4–5 cm³ water per 1–1.5 U (action time 50 min) it can be predicted that the human kidney must lose approximately 261 water per day under the condition of a complete lack of vasopressin. This agreement with the actual observations in diabetes insipidus patients supports the belief that some of the concepts worked out in the alcohol anesthetized rat are valid under circumstances other than the strict conditions of this preparation.

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Zusammenfassung In früheren Experimenten wurden Einzelinjektionen von 0,2–10 E ADH in Alkohol narkotisierte Ratten gemacht und die Wassermenge bestimmt, die während der antidiuretischen Phase rückresorbiert wurde. Die Dosis-Antwort-Kurve hatte den Charakter einer Sättigungskurve mit einem praktisch linearen Anstieg bis 1–1,5 E. Der antidiuretische Effekt war bei einer Injektion von 4–6 E nicht deutlich größer als bei der kleineren Dosis, gleichzeitig fanden sich 75% der injizierten ADH-Menge im Urin der antidiuretischen Phase. Es wurde geschlossen, daß während einer Einzelinjektion von ADH 1–1,5 E fast augenblicklich von Receptoren der Tubuluswand gebunden und dann während des langssamen Prozesses der Wasserresorption inaktiviert werden, während das überschüssige ADH im Urin ausgeschieden wird. Schätzungsweise war 1 E ADH erforderlich, um 5 cm³ Wasser rückzuresorbieren. Die für den Resorptionsvorgang erforderliche Zeit war relativ kurz bei hoher Resorptionsrate und umgekehrt.In den vorliegenden Untersuchungen wurden die Einzelinjektionen mit 20 E wiederholt. Die höhere Dosis erlaubte, die antidiuretische Aktivität (ADA) in drei aufeinanderfolgenden Urinportionen der antidiuretischen Phase getrennt zu bestimmen. Das Resultat bestätigte die Arbeitshypothese.1. Die mit 20 E Pitressin erzielte ADA von 4 cm³ war nicht größer, sondern (nicht signifikant) kleiner als diejenige, die in den früheren Versuchen mit 5 E Pitressin oder 1 E Tonephin gefunden wurden.2. 95±15% der injizierten ADA erschienen im Urin. Das heißt, die Differenz zwischen den 20 injizierten E und den 18,5–19 E, die nach Abzug der vermutlich an der Tubuluswand gebundenen 1–1,5 E ausgeschieden wurden, war zu klein, um mit unserem Bioassay entdeckt zu werden.3. Unter der Annahme, daß 1 E Pitressin verbraucht wurde für die Resorption von ungefähr 4 cm³ Wasser, kann ein Vasopressin-Wasser-Äquivalent von ungefähr 1 Mol Vasopressin für 10⁸ Mol Wasser errechnet werden.4. Die durch die Niere ausgeschiedene Vasopressin-Menge folgt einer e-Funktion mit einer Halbwertszeit von 5 min.5. Die Vasopressin-Clearance beträgt ungefähr 1,0 cm³/min · Ratte und liegt somit wenig unter der Inulin-Clearance (1,2 cm³/min · Ratte). Diese Tatsache legt die Vermutung nahe, daß das überschüssige Vasopressin durch einfache Filtration ausgeschieden wird.6. Wenn man unter Berücksichtigung der unterschiedlichen Nierengewichte den ADH-Bedarf der 200mal schwereren Menschenniere schätzt, so kommt man auf 200–300 E. Setzt man ein Vasopressin-Wasser-Äquivalent von 4–5 cm³ pro 1–1,5 E ADH bei einer Wirkzeit von 50 min in Rechnung, so sollte die menschliche Niere ca. 261 Wasser pro Tag bei völligem Fehlen von ADH verlieren. Die Übereinstimmung mit dem wirklichen Wert könnte dafür sprechen, daß ein Teil der Resultate, die an der Alkohol-narkotisierten Ratte gewonnen wurden, nicht nur unter den strikten Bedingungen dieses Präparates gelten.

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This work was supported by Contract AF 61 (052)-947 of the USAF School of Aerospace Medicine, European Office of Aerospace Research (OAR), U.S. Air Force and the Deutsche Forschungsgemeinschaft.     

Vasopressin: Secondary immune response and antigen-specific suppressors

A single injection of arginine vasopressin during primary immunization stimulates secondary immune response. Vasopressin decreases the activity of antigen-specific suppressors induced by hyperimmune doses of the antigen. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 60–62, January, 1999     

Vasopressin and conditioned flavor aversion in aged rats

The effect of lysine vasopressin on the performance of young-adult and old rats subjected to a conditioned flavor aversion procedure was studied. Young rats maintained an aversion to a 0.1% saccharin solution significantly longer than did older rats. Treatment with lysine vasopressin (1 μg/kg) during the recovery period prolonged the aversion in both age groups. A single injection of lysine vasopressin prior to the aversion procedure significantly reduced the age difference in extinction. These observations support the hypothesis that age-dependent changes in endogenous vasopressin synthesis or secretion underlie some of the behavioral deficits observed in old animals.     

人血浆精氨酸加压素放射免疫测定及其应用

目的 :建立灵敏、特异的人血浆AVP放射免疫测定法。方法 :用氨胺—T法标记AVP ,BSA终止反应 ,经SephadexG -25柱纯化 ,获高比放射性 125I-AVP ,血浆标本经C18Sep-Pak柱纯化后进行放免分析。结果 :该方法灵敏度为0.7pg,回收率93.5±8.1 % ;批间变异系数13 % ,当血浆AVP浓度为3.0pg/ml和11.0pg/ml时 ,批内变异系数分别为11 %和6.4 %。临床应用结果证实 :隔夜禁饮 ,正常人清晨空腹的血浆渗透压为290.0±7.3mosm/kgH2O时 ,血浆AVP浓度为3.8±1.9pg/ml;本法能准确诊断不适当的抗利尿激素分泌和尿崩症 ,将典型的中枢性尿崩症与其他低渗性多尿症区分开来。结论 :本方法适用于临床及科研。     

Vasopressin and renin response to dehydration in aged rats

Abnormalities in neurohypophyseal function have been postulated to contribute to the alterations in fluid and electrolyte balance observed during aging. In this study, parameters of fluid and electrolyte balance were evaluated during chronic water deprivation in old (30 months) and young (3 months) Fischer 344 rats. The increases in serum vasopressin (VP) and renin concentrations observed in the 3 month animals following chronic water deprivation were absent in the aged rats (p<0.05 and p<0.02, respectively). This occurred in spite of apparently comparable alterations in fluid volume and osmolality (assessed by changes in body weight, hematocrit and plasma osmolality). Relative to body weight, VP content of the neural lobe was significantly reduced and was more severely depleted by dehydration in aged rats than in young rats. Thus, inadequate neurohypophyseal hormone stores may contribute to the inability of the aged animals to attain elevated serum VP concentrations during chronic stimulation. Several parameters of renal function were examined in the aged rats. Although none of the old rats were in renal failure, they all showed some indication of reduced renal function. In spite of renal abnormalities including reduced concentrating capabilities, the old rats did demonstrate a significant antidiuretic response to dehydration. However, with prolonged fluid deprivation, they were unable to attain serum VP or renin concentrations comparable to that achieved by the young rats.     

Vasopressin and renin response to dehydration in aged rats

Abnormalities in neurohypophyseal function have been postulated to contribute to the alterations in fluid and electrolyte balance observed during aging. In this study, parameters of fluid and electrolyte balance were evaluated during chronic water deprivation in old (30 months) and young (3 months) Fischer 344 rats. The increases in serum vasopressin (VP) and renin concentrations observed in the 3 month animals following chronic water deprivation were absent in the aged rats (p<0.05 and p<0.02, respectively). This occurred in spite of apparently comparable alterations in fluid volume and osmolality (assessed by changes in body weight, hematocrit and plasma osmolality). Relative to body weight, VP content of the neural lobe was significantly reduced and was more severely depleted by dehydration in aged rats than in young rats. Thus, inadequate neurohypophyseal hormone stores may contribute to the inability of the aged animals to attain elevated serum VP concentrations during chronic stimulation. Several parameters of renal function were examined in the aged rats. Although none of the old rats were in renal failure, they all showed some indication of reduced renal function. In spite of renal abnormalities including reduced concentrating capabilities, the old rats did demonstrate a significant antidiuretic response to dehydration. However, with prolonged fluid deprivation, they were unable to attain serum VP or renin concentrations comparable to that achieved by the young rats.     

Vasopressin: cellular and molecular aspects of its antidiuretic effect

The paper reviews current data on molecular mechanisms of action of the neuropituitary hormone vasopressin (VP) on the aqueous epithelial permeability of the amphibian renal tubules and urinary bladder. It considers the structure and function of VP receptors, cAMP-dependent cellular events induced by VP, the action of different modulators on the effects of VP, the structure and localization of proteins that water-forming channels within the cellular membranes along the renal tubules. The development of VP sensitivity in ontogenesis is shown to be associated with age-related changes in the membrane receptor complex and with the higher activity of the adenylate cyclase mechanism.